Redox modification of proteins as essential mediators of CNS autophagy and mitophagy

Lizama, Britney N.; McLaughlin, BethAnn

doi:10.1016/j.febslet.2013.06.007

Cited by 33 publications

(24 citation statements)

References 99 publications

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“…ROS generated from mitochondria and NADPH oxidases have been demonstrated to be essential to autophagy activation (2, 29, 30). Increased ROS induce autophagy activation via oxidative modification of proteins that is involved in either the autophagy machinery or autophagic cell signaling (20). Hydrogen peroxide has been shown to oxidize and subsequently inactivate Atg4 during starvation.…”

Section: Discussionmentioning

confidence: 99%

Autophagy in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation

Zhang

Liu

Dull

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation. Am J Physiol Lung Cell Mol Physiol 307: L173-L185, 2014. First published May 16, 2014 doi:10.1152/ajplung.00083.2014.-The inflammatory response is a primary mechanism in the pathogenesis of ventilator-induced lung injury. Autophagy is an essential, homeostatic process by which cells break down their own components. We explored the role of autophagy in the mechanisms of mechanical ventilation-induced lung inflammatory injury. Mice were subjected to low (7 ml/kg) or high (28 ml/kg) tidal volume ventilation for 2 h. Bone marrow-derived macrophages transfected with a scrambled or autophagy-related protein 5 small interfering RNA were administered to alveolar macrophage-depleted mice via a jugular venous cannula 30 min before the start of the ventilation protocol. In some experiments, mice were ventilated in the absence and presence of autophagy inhibitors 3-methyladenine (15 mg/kg ip) or trichostatin A (1 mg/kg ip). Mechanical ventilation with a high tidal volume caused rapid (within minutes) activation of autophagy in the lung. Conventional transmission electron microscopic examination of lung sections showed that mechanical ventilation-induced autophagy activation mainly occurred in lung macrophages. Autophagy activation in the lungs during mechanical ventilation was dramatically attenuated in alveolar macrophage-depleted mice. Selective silencing of autophagyrelated protein 5 in lung macrophages abolished mechanical ventilation-induced nucleotide-binding oligomerization domain-like receptor containing pyrin domain 3 (NLRP3) inflammasome activation and lung inflammatory injury. Pharmacological inhibition of autophagy also significantly attenuated the inflammatory responses caused by lung hyperinflation. The activation of autophagy in macrophages mediates early lung inflammation during mechanical ventilation via NLRP3 inflammasome signaling. Inhibition of autophagy activation in lung macrophages may therefore provide a novel and promising strategy for the prevention and treatment of ventilator-induced lung injury. lung injury; autophagy; mechanical ventilation; inflammasome; macrophage MECHANICAL VENTILATION not only saves the lives of patients with respiratory failure but also initiates and exacerbates lung injury known as ventilator-induced lung injury (VILI), which in turn contributes to patient morbidity and mortality (11). VILI is characterized by an influx of inflammatory cells, increased pulmonary vascular permeability, and endothelial and epithelial cell death. The release of proinflammatory cytokines by lung cells in response to mechanical stretch is a crucial event for initiation and/or potentiation of VILI and may cause systemic inflammatory response and multiple system organ failure (4,22,35). The alveolar macrophages (AMs) (5, 7, 26), neutrophils (42), alveolar epithelium (35), and endothelium (10) are all involved in the production of proinflammatory cytokines during mechanical ...

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Section: Discussionmentioning

confidence: 99%

Autophagy in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation

Zhang

Liu

Dull

et al. 2014

American Journal of Physiology-Lung Cellular and Molecular Phys

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“…Even though posttranslational protein modifications represent a molecular hallmark of pathologies associated with redox dysregulation such as neurodegeneration, atherosclerosis, and diabetes, only limited research has examined the occurrence of protein epitopes derived from chemical adduction by RCS in human skin in response to solar UVR [29, 44, 45]. Remarkably, formation of MDA-derived protein adducts in skin exposed to solar UVR has not been investigated before, even though these epitopes are known to accumulate in tissue under conditions of pathologic oxidative stress [46–48].…”

Section: Discussionmentioning

confidence: 99%

Malondialdehyde-derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue

Williams

Bermudez

Park

et al. 2014

Journal of Photochemistry and Photobiology B: Biology

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Cutaneous exposure to solar ultraviolet radiation (UVR) is a causative factor in photoaging and photocarcinogenesis. In human skin, oxidative stress is widely considered a key mechanism underlying the detrimental effects of acute and chronic UVR exposure. The lipid peroxidation product malondialdehyde (MDA) accumulates in tissue under conditions of increased oxidative stress, and the occurrence of MDA-derived protein epitopes, including dihydropyridine-lysine (DHP), has recently been substantiated in human skin. Here we demonstrate for the first time that acute exposure to sub-apoptogenic doses of solar simulated UV light (SSL) causes the formation of free MDA and protein-bound MDA-derived epitopes in cultured human HaCaT keratinocytes and healthy human skin. Immunohistochemical staining revealed that acute exposure to SSL is sufficient to cause an almost twenty-fold increase in general MDA- and specific DHP-epitope content in human skin. When compared to dose-matched solar simulated UVA, complete SSL was more efficient generating both free MDA and MDA-derived epitopes. Subsequent tissue microarray (TMA) analysis revealed the prevalence of MDA- and DHP-epitopes in nonmelanoma skin cancer (NMSC). In squamous cell carcinoma tissue, both MDA- and DHP-epitopes were increased more than three-fold as compared to adjacent normal tissue. Taken together, these date demonstrate the occurrence of MDA-derived epitopes in both solar UVR-exposed healthy human skin and NMSC TMA tissue; however, the potential utility of these epitopes as novel biomarkers of cutaneous photodamage and a functional role in the process of skin photocarcinogenesis remain to be explored.

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“…154 ROS and/or redox imbalance-sensitive PTMs of metabolic enzymes, oncogenes, tumor-suppressor transcription factors and signaling molecules may play considerable roles in metabolic reprogramming. The PTMs on these proteins identified to be modulated by redox changes in cancer cells are phosphorylation, nitration, cysteine oxidation, glutathionylation, acetylation, methylation and SUMOylation (Figure 3), 19, 155, 156, 157, 158, 159 and studies showed acetylation of most enzymes functioning in glycolysis and the Krebs cycle. 160, 161 Oxidative stress induced with menadione affects the activities of core metabolic enzymes, such as PDH, IDH, fumarase, GAPDH, malic enzyme and citrate synthase, as well as levels of various metabolites from glycolysis and the Krebs cycle.…”

Section: Influence Of Oxidative Stress On Metabolic Enzymesmentioning

confidence: 99%

ROS homeostasis and metabolism: a critical liaison for cancer therapy

Kim

Bae³

2016

Exp Mol Med

244

147

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Evidence indicates that hypoxia and oxidative stress can control metabolic reprogramming of cancer cells and other cells in tumor microenvironments and that the reprogrammed metabolic pathways in cancer tissue can also alter the redox balance. Thus, important steps toward developing novel cancer therapy approaches would be to identify and modulate critical biochemical nodes that are deregulated in cancer metabolism and determine if the therapeutic efficiency can be influenced by changes in redox homeostasis in cancer tissues. In this review, we will explore the molecular mechanisms responsible for the metabolic reprogramming of tumor microenvironments, the functional modulation of which may disrupt the effects of or may be disrupted by redox homeostasis modulating cancer therapy.

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Redox modification of proteins as essential mediators of CNS autophagy and mitophagy

Cited by 33 publications

References 99 publications

Autophagy in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation

Autophagy in pulmonary macrophages mediates lung inflammatory injury via NLRP3 inflammasome activation during mechanical ventilation

Malondialdehyde-derived epitopes in human skin result from acute exposure to solar UV and occur in nonmelanoma skin cancer tissue

ROS homeostasis and metabolism: a critical liaison for cancer therapy

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